This is a revised Academic research Enhancement Award (AREA) application from Dr. Wade Waters that aims to investigate the immune mechanisms underlying the development of inflammatory bowel disease in mice infected with Cryptosporidium parvum. TCR-alpha deficient mice develop IBD spontaneously at 20 weeks of age, but the process is accelerated by infection with C. parvum. The questions pending are what are the mediators of this process and is C. parvum required to persist in order for IBD to develop. There are two hypotheses that would be tested in four specific aims. The first hypothesis is that a dysregulated gamma-delta T cell response to inflammation induced by C. parvum infection results in a B cell-mediated IBD in TCR-alpha deficient mice. This would be tested in three specific aims: 1. Characterization of gamma-delta cells from infected mice; 2) adoptive transfer of gamma-delta cells from infected mice to non-infected mice in order to test their ability to confer disease; 3) assess the role of B cells in TCR-alpha deficient mice by crossing them with JH-/- mice and infecting double knock-out mice with C. parvum. The second hypothesis is that transient C. parvum infection of TCR alpha deficient mice results in chronic IBD. These experiments would be conducted by treating infected mice with a spermine analog which cures infection and assessing the development of IBD.